Lynch syndrome

for the gynaecologist

Lynch syndrome is an inherited predisposition to several cancer types,
including endometrial, colorectal and ovarian cancer. The gynaecologist has a
crucial role in diagnosing Lynch syndrome and advising women of its implications.

With the emerging integration of genomic medicine into routine clinical

practice, obstetricians and gynaecologists must become more familiar with
common genetic conditions, such as Lynch syndrome

What is Lynch syndrome?

Lynch syndrome is an autosomal Lynch syndrome may

dominant cancer predisposition occur in up to
syndrome arising from a

1 278
dysfunctional DNA mismatch
repair (MMR) system in
people
Up to 95% of Lynch
syndrome carriers making it the most
are unaware common inherited
cause of cancer

Lynch syndrome arises from inherited mutations, known as pathogenic

variants, affecting MLH1, MSH2, MSH6 and PMS2, the MMR genes
responsible for ensuring fidelity during DNA replication

Cumulative lifetime risks of cancer in Lynch syndrome

Ovarian Endometrial Colorectal

Up to 17% Up to 57% Up to 47%

Women with Lynch syndrome should be seen at around the age of 25 by an expert
gynaecologist to learn about the red flag symptoms of cancer, discuss
family planning and explore cancer risk-reducing strategies

Screening Risk-reducing
and diagnosis strategies
The National Institute for Health and Hysterectomy
Care Excellence now recommends that
all women with endometrial cancer are The lifetime risk of gynaecological cancer is
screened for Lynch syndrome sufficiently high to offer total hysterectomy +/-
bilateral salpingo-oophorectomy for women with
Lynch syndrome who have completed childbearing.

Tumour-based testing
Tumour-based testing does not identify people
with Lynch syndrome; it stratifies their risk for
the condition.
Immunohistochemistry
Immunohistochemistry tests for loss of MMR
protein expression (MMR deficiency). There is a
relative lack of specificity, associated with somatic
loss of MMR expression.
Microsatellite instability analysis
Microsatellites are repeated DNA motifs.
Instability is a marker of hypermutation, as seen
in Lynch syndrome-associated tumours. If
microsatellite instability is high, Lynch syndrome
is more likely.
Germline testing
Involving genomic testing of the patient, germline
testing is the only way in which a Lynch syndrome
diagnosis can be made. It is done using next-
generation sequencing, is expensive and can only
be done in specialist centres.
Hormone therapy
The oral contraceptive pill reduces the risk of
sporadic ovarian and endometrial cancer, and the
levonorgestrel-releasing intrauterine system
reduces the risk of endometrial cancer in the
general population, so it is thought these may also
reduce cancer risk in Lynch syndrome.
Aspirin
Aspirin has been shown to reduce the risk of cancer
in Lynch syndrome. Trials to determine the best
dose of aspirin for cancer prevention are ongoing.
Lifestyle modifications
While few studies have specifically explored the
effect of lifestyle choices on cancer risk in Lynch
syndrome, smoking cessation, maintaining
a healthy body mass index and increased exercise
are thought sensible.
Gynaecological surveillance
There is currently no strong evidence to support
gynaecological surveillance for the early detection
of gynaecological cancer in Lynch syndrome.

The future...
Novel strategies are being tested to harness the Lynch syndrome patient’s own immune
system to prevent cancers through vaccination. Novel diagnostic methods, with the
potential for complete automation, are in development; such technologies would simplify
and reduce the costs of Lynch syndrome screening and diagnostic pathways.

This is a summary of a review published in TOG. For further details on Lynch

syndrome, please read the full article:
Ryan NAJ, McMahon RFT, Ramchander NC, Seif MW,
Evans DG, Crosbie EJ. Lynch syndrome for the gynaecologist.
The Obstetrician & Gynaecologist 2021;
https://doi.org/10.1111/tog.12706

onlinetog.org